NM_018652.5:c.724C>T

Variant names:

• chr15-72661531-C-T
• rs1331525123
• NM_018652.5:c.724C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018652.5(GOLGA6B):​c.724C>T​(p.Arg242Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000031 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.952
• Publications: 0 publications found

Genes affected

GOLGA6B (HGNC:32205): (golgin A6 family member B) This gene is found in a large, low copy repeat sequence or duplicon that is found in multiple copies, which are greater than 90% similar, on chromosome 15. Duplicons are associated with deletions, inversions and other chromosomal rearrangements that underlie genomic disease. This gene is a member of the golgin gene family, whose protein products localize to the Golgi apparatus. The majority of the related gene copies are thought to be transcribed pseudogenes. It is not known whether this gene is a pseudogene or if it encodes a golgin protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27670932).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018652.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	NM_018652.5	MANE Select	c.724C>T	p.Arg242Trp	missense	Exon 9 of 18	NP_061122.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	ENST00000421285.4	TSL:1 MANE Select	c.724C>T	p.Arg242Trp	missense	Exon 9 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.718C>T	p.Arg240Trp	missense	Exon 9 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000310 AC: 4 AN: 129112 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000659

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000535 AC: 3 AN: 56032 AF XY: 0.0000711

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000302 AC: 30 AN: 992486 Hom.: 0 Cov.: 14 AF XY: 0.0000278 AC XY: 14 AN XY: 503564

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000850 AC: 2 AN: 23516

American (AMR) AF: 0.00 AC: 0 AN: 36878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21216

East Asian (EAS) AF: 0.00 AC: 0 AN: 36124

South Asian (SAS) AF: 0.00 AC: 0 AN: 72700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34314

Middle Eastern (MID) AF: 0.000319 AC: 1 AN: 3138

European-Non Finnish (NFE) AF: 0.0000361 AC: 26 AN: 719930

Other (OTH) AF: 0.0000224 AC: 1 AN: 44670

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000333067), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000310 AC: 4 AN: 129112 Hom.: 0 Cov.: 19 AF XY: 0.0000484 AC XY: 3 AN XY: 61948

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32202

American (AMR) AF: 0.00 AC: 0 AN: 13114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3084

East Asian (EAS) AF: 0.00 AC: 0 AN: 4768

South Asian (SAS) AF: 0.00 AC: 0 AN: 3692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000659 AC: 4 AN: 60696

Other (OTH) AF: 0.00 AC: 0 AN: 1600

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.95
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.039
Sift	Uncertain	0.019	D
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.36		Loss of disorder (P = 0.0048)
MVP		0.11
ClinPred		0.40	T
GERP RS		0.39
Varity_R		0.10
gMVP		0.21
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1331525123; hg19: chr15-72953872;